This invention relates to a method for producing a pixelated, thin-film-based, fluid-assay, active-matrix structure. More particularly, it pertains to a method for producing a row-and-column micro-structure array of active, remotely individually digitally-addressable assay pixels which have been prepared on a supporting substrate, each with (a) an included assay sensor (at least one) possessing an assay site (at least one), and (b) an also included digitally-addressable, electromagnetic field-creating structure. This field-creating structure is energizable to bathe the associated pixel with an ambient, exclusively within-pixel-generated electromagnetic field which is one or more of a field of light, a field of heat, and a non-uniform electrical field. On a pixel-by-pixel basis, in accordance with preferred and best mode practice of the invention, and utilizing digital-computer-implemented, pixel-specific digital addressing, the pixels' respective assay sites are exclusively-internally assay-affinity functionalized to possess respective assay-material-specificity so as each to have a defined, specific affinity, i.e., an attraction, for at least one kind of a fluid-assay material.
Preferably, the invention takes the form of a method for creating a relatively inexpensive, consumer-level-affordable, thin-film-based. assay structure which features a low-cost substrate that will readily accommodate low-cost, and preferably “low-temperature-condition”, fabrication thereon of substrate-supported matrix-pixel “components”: “Low temperature” is defined herein as a being a characteristic of processing that can be done on substrate material having a transition temperature (Tg) which is less than about 850° C., i.e., less than a temperature which, if maintained during sustained material processing, would cause the subject material to lose dimensional stability. Accordingly, while the matrix-pixel technology which is involved with practice of the methodology of this invention, if so desired, can be implemented on more costly supporting silicon substrates, the preferred supporting substrate material employed in the practice of the invention is one made of lower-expense glass or plastic materials. The terms “glass” and “plastic” employed herein to describe a preferred substrate material should be understood to be referring also to other suitable “low-temperature materials. Such substrate materials, while importantly contributing on one level to relatively low, overall, end-product cost, also allow specially for the compatible employment, with respect to the fabrication of supported pixel structure, of processes and methods that are based on amorphous, micro-crystal and polysilicon thin-film-transistor (TFT) technology. In particular, these substrate materials uniquely accommodate the use of the just-mentioned, low-temperature TFT technology in such a way that electrical, mechanical and electromagnetic field-creating devices—devices that are included variously in the structure produced by the invention—can be fabricated simultaneously in a process flow which is consistent with the temperature tolerance of such substrate materials.
Regarding the preference herein for the use of low-temperature TFT technology, and briefly describing aspects of that technology, low-temperature TFT devices are formed through deposition processes that deposit silicon-based (or other-material-based, as mentioned below herein, and as referred to at certain points within this text with the expression “etc.”) thin film semiconductor material (which, for certain applications, may, of course, later be laser crystallized). This is quite different from classic silicon CMOS device technology that utilizes a single-crystal silicon wafer bulk material as its semiconductor material. While the resulting TFT devices may not have the switching speed and drive capability of transistors formed on single-crystal substrates, TFT transistors can be fabricated cheaply with a relatively few number of process steps. Further, thin-film deposition processes permit TFT devices to be formed on alternate substrate materials, such as transparent glass substrates, for use, as an example, in liquid crystal displays. In this context, it will be understood that low-temperature TFT device fabrication may variously involve the use typically of amorphous Si (a-Si), of micro-crystalline Si, and or of polycrystalline Si formed by low-temperature internal crystalline-structure processing of amorphous Si. Such processing is described in U.S. Pat. No. 7,125,451 B2, the contents of which patent are hereby incorporated herein by reference.
Further in accordance with preferred and best mode, preferably “silicon on glass or plastic” practice features of the invention, pixel functionalization may be performed under circumstances wherein it is aided by the presence and use, in each pixel, of the included pixel-bathing electromagnetic field-creating structure which is, when so used, remotely and controllably energized under the management of an appropriate digital computer, to generate (or produce), entirely from within the pixel, and to bathe the associated, pixel-included assay sensor and its possessed assay site(s) with, such a field (light, heat and/or non-uniform electrical).
Beyond the specific practice of the present invention, this same field-creating structure has later utility, where appropriate, in relation to participating selectively in the reading-out of ultimately achieved, completed-assay results. More will be said about this invention-enabled later utility shortly.
Digitally addressed, pixel-by-pixel functionalization allows for the production of highly specialized and individualized fluid-material assays. Such functionalization, performed in the context of also employing, as an aid, the mentioned electromagnetic field-creating structure, enables a very high, selective versatility to be associated with finally functionalized pixels. Additionally, and as will be more fully explained later herein, this same, per-pixel, digitally-addressable electromagnetic field-creating structure opens the door to permitting a number of highly specialized assay-result output reading practices.
The present invention, utilizing the above-mentioned low-temperature TFT and “Si on glass or plastic substrate” technology, thus takes the form of a method for creating an extremely versatile and relatively low-cost digitally-addressable assay structure, also referred to herein interchangeably as a micro-structure. As will become apparent from the invention description which is provided herein, the structure created by the methodology of this invention is one which is providable, as a singularity, to a user, in a status which enables that user to perform one, or even plural different (as will be explained), type(s) of fluid-material assay(s). It is also a structure which enables the useful reading out of completed assay results completely on a precision, pixel-by-pixel basis.
As will be seen, the methodology which is contributed to the state of the relevant sensor assay art by the present invention is a very high-level methodology. In this context, it consists of a unique, high-level organization of steps which are cooperatively linked to produce a unique fluid-assay structure. Detailed features of the several high-level steps involved in the practice of this invention are, or may be, drawn from well-known and conventional practices aimed at producing various micro-structure devices and features, such as semiconductor matrices, or arrays. The invention does not reside in, or include, any of these feature details. Rather, it resides in the overall arrangement of steps that are capable of leading to the fabrication of the desired, end-result assay micro-structure mentioned above.
With respect to the concept of assay-site functionalization, except for the special features enabled by practice of the present invention that relate (a) to “pixel-specific” functionalization, and (b) possible functionalization under the influence of an assay-site-bathing, ambient electromagnetic field of a selected nature, assay-site functionalization is in all other respects essentially conventional in practice. Such functionalization is, therefore, insofar as its conventional aspects are concerned, well known to those generally skilled in the relevant art, and not elaborated herein, but for a brief mention later herein noting the probable collaborative use, in many functionalization procedures, of conventional flow-cell assay-sensor-functional processes.
While ultimately-enabled functionalization specificity for a particular selected assay site (resident within a given pixel), in accordance with practice of the present invention in certain instances, is generally and largely controlled by ambient “bathing” of that site with selected-nature electromagnetic-field energy received from the earlier-mentioned, and of course appropriately positioned electromagnetic field-creating structure, it turns out that “site-precision” functionalization-bathing specificity is not a critical operational factor. In other words, it is entirely appropriate if the entirety of a pixel is field-bathed, and thereby becomes ultimately “overall functionalized”. Accordingly, terminology referring to pixel functionalization and to assay-site functionalization is used herein interchangeably.
While there are many ways in which the core characteristics of this methodologic invention may be visualized and understood, one good way to accomplish this is to focus attention upon the important characteristics of the intended, end-result product of the proposed assay-structure-producing methodology. Accordingly, we lead into the description of this methodologic invention through a description of that end-result product, with reference made to several embodiments/modifications of such a product. The methodologic steps of the invention are set forth following this product discussion.
One of the first important things to note about the subject end-result product is that it takes the form of a micro-structure pixelated array, or matrix, of active pixels which are designed to be individually, i.e., pixel-specifically, addressed and accessed, for at least two important purposes, by a digital computer. The first of these purposes is to enable selective functionalization of assay sites in pixels to become responsive to particular fluid-assay materials. The second involves enabling user-selectable access to functionalized pixels to obtain output readings of responses generated by those pixels regarding the result(s) of a performed fluid-material assay. In this context, the structure generally created by the methodology of this invention allows for selective characterization of an entire matrix array, or even simply portions of such an array, for the performance of a specific, or plural specific (different or same), user-chosen fluid-material assay(s).
A full description of the preferred and best mode methodology of the invention herein will follow (a) a completion of this introductory text, (b) the then-presented Description of the Drawings, and (c) the thereafter-presented, detailed, end-result product description.
Before continuing, however, certain definitions relating to terminology employed herein are set forth.
The term “active-matrix” as used herein refers to a pixelated structure wherein each pixel is controlled by and in relation to some form of digitally-addressable electronic structure, which structure includes digitally-addressable electronic switching structure, defined by one or more electronic switching device(s), operatively associated, as will be seen, with also-included pixel-specific assay-sensor structure and pixel-bathing electromagnetic field-creating, or functionalizing, structure—all formed preferably by low-temperature TFT and Si technology as mentioned above.
The term “bi-alternate” refers to a possible, selectable matrix condition enabled by practice of the present invention, wherein every other pixel in each row and column of pixels is selectively commonly functionalized for one, specific type of fluid-material assay. This condition effectively creates, across the entire area of an overall matrix made by practice of the invention, two differently and/or separately functionalized, lower-pixel-count submatrices of pixels (what can be thought of as a two-assay, single-overall-matrix condition).
The term “tri-alternate” refers to a similar condition, but one wherein every third pixel in each row and column is selectively commonly functionalized for one, specific type of a fluid-material assay. This condition effectively creates, across the entire area of an overall matrix, three, differently and/or separately functionalized, lower-pixel-count submatrices of pixels (what can be thought of as a three-assay, single-overall-matrix condition).
Individual digital addressability of each pixel permits these and other kinds of lower-pixel-count, submatrix functionalization options, if desired.
Other kinds of submatrices are, of course, possible, and one other type of submatrix arrangement is specifically mentioned hereinbelow.
Whenever the present invention is practiced to create a submatrix functionalization of an overall matrix, that approach, depending upon functionalization “strategy”, enables either (a) several, successive same-assay-material matrix-assay uses to take place with the same overall matrix, or (b) several successive different-assay-material submatrix-assay uses to occur, also employing the same overall matrix.
It should be apparent also that the implementation, in the practice of the invention, of different submatrix-functionalization pixel distributions with respect to one-only, or to different, matrix structure(s) can enable a end user to perform selected assays with such different distributions at different pixel-distribution “granularities”.
Each prepared “precursor” pixel, which is an active-matrix pixel as that language is employed herein, includes, as was mentioned, at least one, electronically, digitally-addressable assay sensor which is designed to possess, or host, at least one functionalized, electronically digitally-addressable fluid-assay site that will have and display an affinity for a selected, specific fluid-assay material. Each such pixel also includes, as earlier indicated, an “on-board”, digitally-addressable, assay-site-bathing (also referred to as “pixel-bathing”), preferably thin-film, electromagnetic-field-creating structure which, among other things, is controllably energizable, as will be explained, (a) to assist in the functionalization of such a site for the performance of a specific kind of fluid-material assay, and (b) to assist (where appropriate) in the later output reading of the result of a particular assay. This pixel-bathing, electronic, field-creating structure is capable, via the inclusion therein (by way of practice of the present invention) of suitable, different, field-creating subcomponents, and in accordance with aspects of the present invention, of producing, as a pixel-bathing, ambient field environment within its respective, associated pixel, any one or more of (a) an ambient light field, (b) an ambient heat field, and (c) an ambient non-uniform electrical field.
In the proposed row-and-column arrangement of assay pixels prepared in accordance with the practice of the present invention, each pixel includes a least one, and may include more than one, assay sensor(s), with each such assay sensor being ultimately functionalized to host, or possess, at least one, but selectively plural, assay-material-specific assay sites that are functionalized appropriately for such materials.
Additionally, and with respect to the issue of ultimate versatility as it relates to the concept regarding submatrices, it is possible to create (i.e., to functionalize) plural, different, internally unified (all internally alike) subareas (i.e., unified lower-pixel-count submatrices defined by next-adjacent, side-by-side pixels) within an overall, entire matrix, and to functionalize such pixels to respond to one specific type of fluid-assay material, with each such different, internally unified area being functionalized to respond to respective, different assay materials.
It should be understood, regarding functionalization, which, for DNA assay purposes, involves DNA probe-building, that while the end-result structure created by practice of the present invention is built in such a fashion that all addressable, pixel-bathing field-creating functionalization subcomponents within each pixel are remotely digitally addressable to assist in pixel, probe-building functionalization, actual overall functionalization of an assay site on a pixel assay sensor may involve, additionally, and as was mentioned briefly earlier, the utilization of conventional flow-cell processes in order to implement a full correct functionalization procedure. For example, where an assay site in such a pixel is to become functionalized to respond in a DNA-oligonucleotide-probe-type assay, conventional flow-cell technology may be used, in cooperation with probe-building functionalization assistance provided by the on-board field-creating structure, to carry out such full assay-site, DNA probe-building functionalization.
As will become apparent, one especially interesting feature of a matrix micro-structure produced by practice of this invention is that it introduces the possibility of deriving assay-result data, including kinetic assay-reaction data, effectively on or along plural, special axes not enabled by prior art devices. For example, and with respect to the performance, or performances, of a selected, particular type of fluid-material assay, pixels in a group of pixels contained in a full matrix, or in a lower-pixel-count submatrix, may be functionalized utilizing plural different levels, or intensities, of functionalization-assist fields, such as intensity-differentiated heat and/or non-uniform electrical fields. Such differentiated field-intensity functionalization can yield assay-result output information regarding how an assay's results are affected by “field-differentiated” pixel functionalization. Similarly, assay results may be observed by reading pixel output responses successively under different, pixel-bathing ambient electromagnetic field conditions that are then presented seriatim to information-outputting pixels.
Further in relation to the versatile matrix utility enabled in a finished matrix array ultimately by practice of methodology of the present invention, following the performance of an assay with that array, and with respect specifically to the reading-out of completed-assay response information, time-axis output data may easily be gathered on a pixel-by-pixel basis via pixel-specific, digital output sampling.
Regarding the making of a matrix micro-structure as proposed by the present invention, an important point to note, as suggested earlier herein, is that the particular details of the processes, procedures and specific methodologic steps which are employed specifically to fabricate the subject micro-structure may be drawn entirely from conventional micro-array fabrication practices, such as the earlier-mentioned TFT, Si, low-temperature, and low-cost-substrate technology practices, well known to those generally skilled the art. Accordingly, while the high-level, overall organization of cooperative steps proposed by the invention is unique, the details of these steps, which form no part of the present invention, are not set forth herein. Those generally skilled in the relevant art will understand, from a reading of the present specification text, taken along with the accompanying drawing figures, exactly how to practice the present invention, i.e., will be fully enabled by the disclosure material in this text and the accompanying drawings to practice the invention in all of its unique facets.
The various features and advantages of the methodology of the present invention, including those generally set forth above, will become more fully apparent as the description of the invention which now follows below in detail is read in conjunction with the accompanying drawings.